Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

Addressing Cancer Disparities via Community Network Mobilization and Intersectoral Partnerships: A Social Network Analysis

Community mobilization and collaboration among diverse partners are vital components of the effort to reduce and eliminate cancer disparities in the United States. We studied the development and impact of intersectoral connections among the members of the Massachusetts Community Network for Cancer Education, Research, and Training (MassCONECT). As one of the Community Network Program sites funded by the National Cancer Institute, this infrastructure-building initiative utilized principles of Community-based Participatory Research (CBPR) to unite community coalitions, researchers, policymakers, and other important stakeholders to address cancer disparities in three Massachusetts communities: Boston, Lawrence, and Worcester. We conducted a cross-sectional, sociometric network analysis four years after the network was formed. A total of 38 of 55 members participated in the study (69% response rate). Over four years of collaboration, the number of intersectoral connections reported by members (intersectoral out-degree) increased, as did the extent to which such connections were reported reciprocally (intersectoral reciprocity). We assessed relationships between these markers of intersectoral collaboration and three intermediate outcomes in the effort to reduce and eliminate cancer disparities: delivery of community activities, policy engagement, and grants/publications. We found a positive and statistically significant relationship between intersectoral out-degree and community activities and policy engagement (the relationship was borderline significant for grants/publications). We found a positive and statistically significant relationship between intersectoral reciprocity and community activities and grants/publications (the relationship was borderline significant for policy engagement). The study suggests that intersectoral connections may be important drivers of diverse intermediate outcomes in the effort to reduce and eliminate cancer disparities. The findings support investment in infrastructure-building and intersectoral mobilization in addressing disparities and highlight the benefits of using CBPR approaches for such work

Pre-competition habits and injuries in Taekwondo athletes

BACKGROUND: Over the past decade, there has been heightened interest in injury rates sustained by martial arts athletes, and more specifically, Taekwondo athletes. Despite this interest, there is a paucity of research on pre-competition habits and training of these athletes. The purpose of this pilot study was to assess training characteristics, competition preparation habits, and injury profiles of Taekwondo athletes. METHODS: A retrospective survey of Canadian male and female Taekwondo athletes competing in a national tournament was conducted. Competitors at a Canadian national level tournament were given a comprehensive survey prior to competition. Items on training characteristics, diet, and injuries sustained during training and competition were included. Questionnaires were distributed to 60 athletes. RESULTS: A response rate of 46.7% was achieved. Of those that responded, 54% dieted prior to competition, and 36% dieted and exercised pre-competition. Sixty-four percent of the athletes practised between 4–6 times per week, with 54% practicing 2 hours per session. Lower limb injuries were the most common (46.5%), followed by upper extremity (18%), back (10%), and head (3.6%). The majority of injuries consisted of sprains/strains (45%), followed by contusions, fractures, and concussions. More injuries occurred during training, including 59% of first injuries. CONCLUSION: More research needs to be conducted to further illustrate the need for appropriate regulations on weight cycling and injury prevention

Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment

Collective investments for pension savings: Lessons from Singapore's central provident fund scheme

opinions are solely those of the authors who acknowledge research support from the Wharton-SM

General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress.</p> <p>Method</p> <p>Between September 1^stand 30^th, 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28.</p> <p>Results</p> <p>More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008).</p> <p>Conclusions</p> <p>A significant proportion of HCWs experienced moderately high anxiety about the pandemic, and their degree of worry was an independent correlate of psychological distress. Since perceived sufficiency of information about the A/H1N1 influenza prognosis was associated with reduced degree of worry, hospital managers and consultation-liaison psychiatry services should try to provide for HCWs' need for information, in order to offer favourable working conditions in times of extreme distress, such as the current and future pandemics.</p

Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.

Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity

‘Fractional Recovery’ Analysis of a Presynaptic Synaptotagmin 1-Anchored Endocytic Protein Complex

BACKGROUND: The integral synaptic vesicle protein and putative calcium sensor, synaptotagmin 1 (STG), has also been implicated in synaptic vesicle (SV) recovery. However, proteins with which STG interacts during SV endocytosis remain poorly understood. We have isolated an STG-associated endocytic complex (SAE) from presynaptic nerve terminals and have used a novel fractional recovery (FR) assay based on electrostatic dissociation to identify SAE components and map the complex structure. The location of SAE in the presynaptic terminal was determined by high-resolution quantitative immunocytochemistry at the chick ciliary ganglion giant calyx-type synapse. METHODOLOGY/PRINCIPLE FINDINGS: The first step in FR analysis was to immunoprecipitate (IP) the complex with an antibody against one protein component (the IP-protein). The immobilized complex was then exposed to a high salt (1150 mM) stress-test that caused shedding of co-immunoprecipitated proteins (co-IP-proteins). A Fractional Recovery ratio (FR: recovery after high salt/recovery with control salt as assayed by Western blot) was calculated for each co-IP-protein. These FR values reflect complex structure since an easily dissociated protein, with a low FR value, cannot be intermediary between the IP-protein and a salt-resistant protein. The structure of the complex was mapped and a blueprint generated with a pair of FR analyses generated using two different IP-proteins. The blueprint of SAE contains an AP180/X/STG/stonin 2/intersectin/epsin core (X is unknown and epsin is hypothesized), and an AP2 adaptor, H-/L-clathrin coat and dynamin scission protein perimeter. Quantitative immunocytochemistry (ICA/ICQ method) at an isolated calyx-type presynaptic terminal indicates that this complex is associated with STG at the presynaptic transmitter release face but not with STG on intracellular synaptic vesicles. CONCLUSIONS/SIGNIFICANCE: We hypothesize that the SAE serves as a recognition site and also as a seed complex for clathrin-mediated synaptic vesicle recovery. The combination of FR analysis with quantitative immunocytochemistry provides a novel and effective strategy for the identification and characterization of biologically-relevant multi-molecular complexes

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012